Rickettsia parkeri infections diagnosed by eschar biopsy, Virginia, USA.

BACKGROUND: Infection with Rickettsia parkeri is an emerging tick-borne illness, often accompanied by fever and an eschar at the site of tick attachment. We present three cases of R. parkeri in Virginia residents. CASE PRESENTATIONS: Case 1 presented initially afebrile, failed to seroconvert to rickettsial antigens, and was diagnosed by DNA testing of the eschar. Case 2 presented febrile with eschar, no serologies were performed, and was diagnosed by DNA testing of the eschar. Case 3 presented febrile with eschar, serologies were negative for rickettsial antigens, and was diagnosed by DNA testing of the eschar. CONCLUSION: DNA testing of eschars represents an under-utilized diagnostic test and may aid in cases where the diagnosis is not made clinically.

A ketone ester diet increases brain malonyl-CoA and Uncoupling proteins 4 and 5 while decreasing food intake in the normal Wistar Rat.

Three groups of male Wistar rats were pair fed NIH-31 diets for 14 days to which were added 30% of calories as corn starch, palm oil, or R-3-hydroxybutyrate-R-1,3-butanediol monoester (3HB-BD ester). On the 14th day, animal brains were removed by freeze-blowing, and brain metabolites measured. Animals fed the ketone ester diet had elevated mean blood ketone bodies of 3.5 mm and lowered plasma glucose, insulin, and leptin. Despite the decreased plasma leptin, feeding the ketone ester diet ad lib decreased voluntary food intake 2-fold for 6 days while brain malonyl-CoA was increased by about 25% in ketone-fed group but not in the palm oil fed group. Unlike the acute effects of ketone body metabolism in the perfused working heart, there was no increased reduction in brain free mitochondrial [NAD(+)]/[NADH] ratio nor in the free energy of ATP hydrolysis, which was compatible with the observed 1.5-fold increase in brain uncoupling proteins 4 and 5. Feeding ketone ester or palm oil supplemented diets decreased brain L-glutamate by 15-20% and GABA by about 34% supporting the view that fatty acids as well as ketone bodies can be metabolized by the brain.

Recommendations for Welcoming Back Nursing Home Visitors During the COVID-19 Pandemic: Results of a Delphi Panel.

OBJECTIVES: Nursing homes became epicenters of COVID-19 in the spring of 2020. Due to the substantial case fatality rates within congregate settings, federal agencies recommended restrictions to family visits. Six months into the COVID-19 pandemic, these largely remain in place. The objective of this study was to generate consensus guidance statements focusing on essential family caregivers and visitors. DESIGN: A modified 2-step Delphi process was used to generate consensus statements. SETTING AND PARTICIPANTS: The Delphi panel consisted of 21 US and Canadian post-acute and long-term care experts in clinical medicine, administration, and patient care advocacy. METHODS: State and federal reopening statements were collected in June 2020 and the panel voted on these using a 3-point Likert scale with consensus defined as ≥80% of panel members voting "Agree." The consensus statements then informed development of the visitor guidance statements. RESULTS: The Delphi process yielded 77 consensus statements. Regarding visitor guidance, the panel made 5 strong recommendations: (1) maintain strong infection prevention and control precautions, (2) facilitate indoor and outdoor visits, (3) allow limited physical contact with appropriate precautions, (4) assess individual residents' care preferences and level of risk tolerance, and (5) dedicate an essential caregiver and extend the definition of compassionate care visits to include care that promotes psychosocial well-being of residents. CONCLUSIONS AND IMPLICATIONS: The COVID-19 pandemic has seen substantial regulatory changes without strong consideration of the impact on residents. In the absence of timely and rigorous research, the involvement of clinicians and patient care advocates is important to help create the balance between individual resident preferences and the health of the collective. The results of this evidence-based Delphi process will help guide policy decisions as well as inform future research.

Anatomy, Classification, and Management of Ankle Fractures Involving the Posterior Malleolar Fragment: A Literature Review.

The posterior malleolar fragment is frequently involved in rotational ankle fractures, but diagnosis and definitive management remains controversial. Ankle fractures with a posterior malleolar component that are not identified and treated in a timely manner may contribute significantly to future comorbidities, including continued pain, instability, and the development of arthritis. This article highlights the anatomic features of posterior malleolar ankle fractures, the classification schemes used, and discusses the various nonsurgical and surgical methods currently used. LEVEL OF EVIDENCE: Level V, expert opinion.

A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) involves progressive accumulation of amyloid ß-peptide (Aß) and neurofibrillary pathologies, and glucose hypometabolism in brain regions critical for memory. The 3xTgAD mouse model was used to test the hypothesis that a ketone ester-based diet can ameliorate AD pathogenesis. Beginning at a presymptomatic age, 2 groups of male 3xTgAD mice were fed a diet containing a physiological enantiomeric precursor of ketone bodies (KET) or an isocaloric carbohydrate diet. The results of behavioral tests performed at 4 and 7 months after diet initiation revealed that KET-fed mice exhibited significantly less anxiety in 2 different tests. 3xTgAD mice on the KET diet also exhibited significant, albeit relatively subtle, improvements in performance on learning and memory tests. Immunohistochemical analyses revealed that KET-fed mice exhibited decreased Aß deposition in the subiculum, CA1 and CA3 regions of the hippocampus, and the amygdala. KET-fed mice exhibited reduced levels of hyperphosphorylated tau deposition in the same regions of the hippocampus, amygdala, and cortex. Thus, a novel ketone ester can ameliorate proteopathic and behavioral deficits in a mouse AD model.

The effect of pH and free Mg2+ on ATP linked enzymes and the calculation of Gibbs free energy of ATP hydrolysis.

The apparent equilibrium constants, K', of biochemical reactions containing substrates which bind [Mg2+] unequally can be significantly altered by changes in free intracellular [Mg2+]. Intracellular free [Mg2+] can be estimated by measurements of [citrate]/[isocitrate], a ratio known to vary with tissue free [Mg2+]. The combined equilibrium constant for glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and triose phosphate isomerase for the three reactions (K(GG-TPI)') was corrected using new binding constants for dihydroxyacetone-phosphate and 3-phosphoglycerate. The result of this calculation is demonstrated in the calculation of the free energy of ATP hydrolysis. In addition, the dependence of the equilibrium constant for the glutamine synthetase reaction on pH and free [Mg2+] was demonstrated. Furthermore, a theory linking the ΔG' value of mitochondrial complex I−II and the cytosolic ΔG' value of ATP hydrolysis is discussed with evidence from previous publications.